New active paclitaxel glucuronide derivative with improved water solubility.
Poor solubility of paclitaxel constitutes an important limitation to its administration to cancer patients. In order to increase solubility, while preserving cytotoxicity, a new paclitaxel derivative substituted at the 2' position of the side chain was prepared. The first step consisted in the introduction of a glutaryl group at the 2' position by esterification of the free hydroxyl followed by an amidation with 6-amino hexanol previously attached to a glucuronide group. The new water soluble derivative was cytotoxic in vitro against an ovarian teratocarcinoma cell line.
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Department of Biochemistry, Faculty of Medicine, Universite Laval, Ste-Foy, Quebec G1K 7P4, Canada.
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D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D012995:Solubility; D013054:Spectrophotometry, Atomic; D043823:Taxoids; D018243:Teratocarcinoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D020719:Glucuronides; D043823:Taxoids; C420284:glutarylpaclitaxel 6-aminohexanol glucuronide; D017239:Paclitaxel